Cardiac myosin missense mutations cause dilated cardiomyopathy in mouse models and depress molecular motor function.

ABSTRACT: Dilated cardiomyopathy (DCM) leads to heart failure, a leading cause of death in industrialized nations. Approximately 30% of DCM cases are genetic in origin, with some resulting from point mutations in cardiac myosin, the molecular motor of the heart. The effects of these mutations on myosin's molecular mechanics have not been determined. We have engineered two murine models characterizing the physiological, cellular, and molecular effects of DCM-causing missense mutations (S532P and F764L) in the alpha-cardiac myosin heavy chain and compared them with WT mice. Mutant mice developed morphological and functional characteristics of DCM consistent with the human phenotypes. Contractile function of isolated myocytes was depressed and preceded left ventricular dilation and reduced fractional s

SUBMITTER: Schmitt JP 

PROVIDER: S-EPMC1599993 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature